Two Proteins Homologous to the N- and C-terminal Domains of the Bacterial Glycosyltransferase Murg Are Required for the Second Step of Dolichyl-linked Oligosaccharide Synthesis in Saccharomyces cerevisiae

Chantret, Isabelle; Dancourt, Julia; Barbat, Alain; Moore, Stuart

doi:10.1074/jbc.m413941200

Cited by 46 publications

(59 citation statements)

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“…These proteins function as a heterodimer to transfer the second, β1,4--GlcNAc--linked GlcNAc to Dol--PP--GlcNAc (Bickel et al 2005;Chantret et al 2005;Gao et al 2005). Soluble Alg13, assigned to GT Family 1, is the catalytic subunit and associates with membrane--spanning Alg14 at the cytosolic face of the ER membranes (Averbeck et al 2007;).…”

Section: Assembly and Transfer Of The Dol--pp--linked Precursor Oligomentioning

confidence: 99%

“…Soluble Alg13, assigned to GT Family 1, is the catalytic subunit and associates with membrane--spanning Alg14 at the cytosolic face of the ER membranes (Averbeck et al 2007;). Alg13 and 14 are homologous to C and N--terminal domains, respectively, of the bacterial MurG polypeptide, which adds N--acetylmuramic acid to undecaprenol--PP--GlcNAc in peptidoglycan synthesis (Chantret et al 2005).…”

Section: Assembly and Transfer Of The Dol--pp--linked Precursor Oligomentioning

confidence: 99%

“…Assembly and transfer of the Dol-PP-linked precursor oligosaccharide: Steps on the cytoplasmic face of the ER membrane: These steps are (i) transfer of GlcNAc-1-P from UDP-GlcNAc to Dol-P by Alg7, the target of the N-glycosylation inhibitor tunicamycin (Barnes et al 1984), (ii) transfer of b1,4-GlcNAc from UDP-GlcNAc by heterodimeric Alg13/Alg14 (Bickel et al 2005;Chantret et al 2005;Gao et al 2005), (iii) transfer of a b1,4-linked Man by Alg1 (Couto et al 1984), (iv) successive transfer of an a1,3 and an a1,6 Man by Alg2 (O'Reilly et al 2006;Kämpf et al 2009), and (v) transfer of two a1,2-linked Man by Alg11 (Cipollo et al 2001;O'Reilly et al 2006;Absmanner et al 2010). These proteins act in higher-order complexes Noffz et al 2009;File S2).…”

Section: N-glycosylationmentioning

confidence: 99%

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Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

2012

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The wall gives a Saccharomyces cerevisiae cell its osmotic integrity; defines cell shape during budding growth, mating, sporulation, and pseudohypha formation; and presents adhesive glycoproteins to other yeast cells. The wall consists of b1,3-and b1,6-glucans, a small amount of chitin, and many different proteins that may bear N-and O-linked glycans and a glycolipid anchor. These components become cross-linked in various ways to form higher-order complexes. Wall composition and degree of cross-linking vary during growth and development and change in response to cell wall stress. This article reviews wall biogenesis in vegetative cells, covering the structure of wall components and how they are cross-linked; the biosynthesis of N-and O-linked glycans, glycosylphosphatidylinositol membrane anchors, b1,3-and b1,6-linked glucans, and chitin; the reactions that cross-link wall components; and the possible functions of enzymatic and nonenzymatic cell wall proteins. TABLE OF CONTENTS Abstract 775Introduction 777

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Section: Assembly and Transfer Of The Dol--pp--linked Precursor Oligomentioning

confidence: 99%

Section: Assembly and Transfer Of The Dol--pp--linked Precursor Oligomentioning

confidence: 99%

Section: N-glycosylationmentioning

confidence: 99%

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Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

2012

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“…Alg13p lacks any membrane-spanning domains but contains the predicted catalytic domain. Alg13p's predicted tertiary structure is highly similar to the Escherichia coli MurG UDP-GlcNAc transferase involved in peptidoglycan synthesis, as well as other UDP-GlcNAc transferases, but just within the catalytic domain (Bickel et al, 2005;Chantret et al, 2005;Gao et al, 2005). The ER membrane protein Alg14p does not contain any obvious similarity to other GTases, but its predicted structure is related to the putative lipid-acceptor domain at the N-terminal domain of MurG (Bickel et al, 2005;Chantret et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Unlike other GTases that are membrane proteins comprised of single polypeptides, in the vast majority of eukaryotes this enzyme consists of at least two polypeptides, Alg13p and Alg14p. In yeast, both subunits are essential and required for UDP-GlcNAc transferase activity (Bickel et al, 2005;Chantret et al, 2005;Gao et al, 2005;Averbeck et al, 2007). Alg13p lacks any membrane-spanning domains but contains the predicted catalytic domain.…”

Section: Introductionmentioning

confidence: 99%

Alg13p, the Catalytic Subunit of the Endoplasmic Reticulum UDP-GlcNAc Glycosyltransferase, Is a Target for Proteasomal Degradation

Averbeck

Gao

Nishimura

et al. 2008

MBoC

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The second step of dolichol-linked oligosaccharide synthesis in the N-linked glycosylation pathway at the endoplasmic reticulum (ER) membrane is catalyzed by an unusual hetero-oligomeric UDP-N-acetylglucosamine transferase that in most eukaryotes is comprised of at least two subunits, Alg13p and Alg14p. Alg13p is the cytosolic and catalytic subunit that is recruited to the ER by the membrane protein Alg14p. We show that in Saccharomyces cerevisiae, cytosolic Alg13p is very short-lived, whereas membrane-associated Alg13 is relatively stable. Cytosolic Alg13p is a target for proteasomal degradation, and the failure to degrade excess Alg13p leads to glycosylation defects. Alg13p degradation does not require ubiquitin but instead, requires a C-terminal domain whose deletion results in Alg13p stability. Conversely, appending this sequence onto normally long-lived ␤-galactosidase causes it to undergo rapid degradation, demonstrating that this C-terminal domain represents a novel and autonomous degradation motif. These data lead to the model that proteasomal degradation of excess unassembled Alg13p is an important quality control mechanism that ensures proper protein complex assembly and correct N-linked glycosylation.

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X chromosome exome sequencing reveals a novel ALG13 mutation in a nonsyndromic intellectual disability family with multiple affected male siblings

Bissar-Tadmouri

Donahue

Nelson

et al. 2013

American J of Med Genetics Pt A

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X-linked intellectual disability (XLID) is a heterogeneous condition associated with mutations in >100 genes, accounting for over 10% of all cases of intellectual impairment. The majority of XLID cases show nonsyndromic forms (NSXLID), in which intellectual disability is the sole clinically consistent manifestation. Here we performed X chromosome exome (X-exome) sequencing to identify the causative mutation in an NSXLID family with four affected male siblings and five unaffected female siblings. The X-exome sequencing at 88× coverage in one affected male sibling revealed a novel missense mutation (p.Tyr1074Cys) in the asparagine-linked glycosylation 13 homolog (ALG13) gene. Segregation analysis by Sanger sequencing showed that the all affected siblings were hemizygous and the mother was heterozygous for the mutation. Recently, a de novo missense mutation in ALG13 has been reported in a patient with X-linked congenital disorders of glycosylation type I. Our study reports the first case of NSXLID caused by a mutation in ALG13 involved in protein N-glycosylation.

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Two Proteins Homologous to the N- and C-terminal Domains of the Bacterial Glycosyltransferase Murg Are Required for the Second Step of Dolichyl-linked Oligosaccharide Synthesis in Saccharomyces cerevisiae

Cited by 46 publications

References 34 publications

Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

Alg13p, the Catalytic Subunit of the Endoplasmic Reticulum UDP-GlcNAc Glycosyltransferase, Is a Target for Proteasomal Degradation

X chromosome exome sequencing reveals a novel ALG13 mutation in a nonsyndromic intellectual disability family with multiple affected male siblings

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